Asthma affects over 250 million people worldwide, making it one of the most common chronic respiratory conditions. It can cause recurring episodes of wheezing, breathlessness, chest tightness, and coughing, often triggered by allergens, exercise, or environmental factors. For many, asthma leads to frequent hospital visits, missed days at school or work, and ongoing challenges in daily life.
Despite its prevalence, the reasons why some people develop asthma while others do not remain unclear, especially among populations of African-ancestry, who are most affected by the disease.
A new international study in the Journal of Allergy and Clinical Immunology led by researchers at the University of Colorado Anschutz (CU Anschutz) is helping to change that. The team uncovered 17 genes linked to asthma risk in African-ancestry populations, offering new insights into the genetic influences underlying asthma. They also developed resources that can be applied broadly to other studies investigating genetic influences on health outcomes.
“Our study helps to fill important gaps in understanding how genetics may increase or decrease the likelihood of developing asthma,” said Randi K. Johnson, PhD, MPH, assistant professor of biomedical informatics at CU Anschutz School of Medicine. “Our focus on an under-studied and over-burdened population allowed us to make new discoveries, underscoring the importance of representation in biomedical research for correcting disparities and achieving optimal health for all.”
Johnson drove the collaboration spanning institutions across the U.S., the Caribbean, and beyond, including the Colorado School of Public Health, the University of Colorado Boulder, the National Institutes of Health, the University of the West Indies, Johns Hopkins, the University of Chicago, Children’s Hospital Colorado and others. The work was co-led by Sarah D. Slack, information sciences senior professional in the RKJcollab at the CU Anschutz School of Medicine, and Erika Esquinca, a former master of science student in the Department of Biostatistics and Informatics at the Colorado School of Public Health.
“We are very grateful to the scientists, study leaders, participants, and communities contributing to this international collaboration,” added Johnson. “Their long-standing commitment makes such important work possible.”
Building and Validating Prediction Models
Combining genetic data and gene expression from people of African-ancestry, the research team built models that use genetics to predict gene expression, specifically in tissues that are important for asthma: the nasal epithelium, or lining of the nose, and CD4+ T cells, immune cells that play a role in inflammation. The accuracy of these predictions was highest when applied to studies whose participants had similar ancestral background, a finding that matches what prior studies have shown. While more than 50 expression prediction databases have been developed using majority European-ancestry populations, this study increases those available from majority African-ancestry background from two to four. Since gene expression data from key tissues is hard to obtain, especially for people of African-ancestry, being able to predict it from more widely available genetic data opens new doors for research.
Linking Genes to Asthma: TWAS
Next, the researchers conducted a transcriptome-wide association study (TWAS), to identify genes that affect the likelihood of developing asthma. The TWAS included >9,000 individuals of African-ancestry – the largest African-ancestry TWAS to date – and identified 17 genes whose expression is associated with asthma risk.
Some genes showed tissue-specific activity, like the gene encoding the known regulator of inflammation, IL33, which was identified in the nasal epithelium, where asthma-related inflammation often begins. Other genes, such as CCNC and FBXW7, were active across multiple tissues, suggesting a broader role in asthma development.
New Tools, Broader Impact
This study represents a major advance in understanding asthma’s genetic foundations, particularly in African-ancestry populations that have long been underrepresented in research despite being disproportionately affected by asthma. By analyzing data from thousands of individuals, the team identified 17 genes that may influence asthma risk, insights that lay the foundation for understanding disparities in asthma prevalence, severity, and treatment.
Slack added, “We hope that asthma researchers – and scientists in other fields – will be able to use these models to answer questions that depend on having the right tissue type and relevant ancestry.”
The researchers have made their expression prediction models for nasal epithelium and CD4+ T cells publicly accessible, doubling the number of available models trained in African-ancestry populations and enabling gene expression prediction in two new tissues. By sharing these resources, they are helping to broaden representation in genetic studies and accelerate progress by enabling others to build upon their work.
.png)
.png)